Objective: The purpose of this study was to investigate the direct effects of thyrotropin-releasing hormone on isolated human myometrium that was obtained during pregnancy and on human umbilical vasculature in vitro.Study design: Isolated human myometrial strips were dissected from biopsy specimens that were obtained at elective cesarean delivery and suspended for isometric recording under physiologic conditions. The effects of cumulative additions of thyrotropin-releasing hormone (10(-9)-10(-4) mol/L) on oxytocin-induced myometrial contractility were evaluated. The effects of thyrotropin-releasing hormone (10(-9)-10(-4) mol/L) on umbilical vessel (artery and vein) resistance in vitro were investigated with the use of isolated ring preparations.Results: Thyrotropin-releasing hormone exerted a significant concentration-dependent relaxant effect on pregnant human myometrial tissue, which ranged from 3.54% (10(-9) mol/L, P=.935) to a net cumulative total of 21.06% (10(-4) mol/L, P<.001). Thyrotropin-releasing hormone also exerted a concentration-dependent relaxant effect on human umbilical vasculature that ranged from 12.51% (10(-9) mol/L, P=.994) to a net cumulative total of 23.27%+/-4.87% (SEM, 10(-4) mol/L, P<.01) in umbilical artery. For umbilical vein, the relaxant effect ranged from 1.80% (10(-9) mol/L, P=.998) to a net cumulative total of 14.64% (10(-4) mol/L, P<.009).Conclusion: Thyrotropin-releasing hormone exerts a significant relaxant effect in human myometrium and in human umbilical vasculature and highlights a potential physiologic role for this neuropeptide in these tissues. These findings have clinical implications for the therapeutic use of thyrotropin-releasing hormone antenatally. (C) 2004 Elsevier Inc. All rights reserved.